Establishing An In Silico Model To Predict The Modification Of Systolic Blood Pressure Reaction To Pharmacological Intervention

BackgroundTreatment with blood pressure lowering drugs decreases cardiovascular risk mostly through blood pressure reduction. Selecting the best drug for a given hypertensive patient is difficult due to the number of drug classes. Current prescription strategy for these drugs relies upon some choice by the physician. The response to these drugs in terms of blood pressure is different from one patient to another.ObjectiveWe used the individual patient data from clinical trials, pooled in the INDANA data set, to explore whether blood pressure reduction was related to the baseline individual characteristics, and quantify these potential associations.MethodsWe used the data from patients with essential hypertension recruited in four randomized placebo-controlled clinical trials [Medical Research Council trial in mild hypertension (MRC35-64), Medical Research Council trial in older adults (MRC65-74). Systolic Hypertension in the Elderly Program (SHEP) and Systolic Hypertension in Europe trial (SYST-EU)]. Thiazide diuretics,β-blocker, and calcium channel blocker, three of six major BP lowering drugs were analyzed. Patients were all with the same first dosage of the drug in each trial. Age, body weight, height, level of TC, SBP and DBP when initialed and at first visit of follow-up, pharmacological treatment, gender, status of smoking, history of myocardium infarction were factors taken into model. Data managed by software SAS. Statistical analyses were performed with SAS and R software. Multiple regression analyses were used to evaluate the relationship between SBP fall and characteristics of patients. Significance threshold to keep an interaction in the model was 0.10, significance level of p<0.05 was used for other analyses. SAS and R developed the same model.ResultsIn all 31 140 patients (mean age 60±11 years,47% men) blood pressure at enrollment averaged 168.0mmHg systolic and 92.1mmHg diastolic. Among individual trials the SBP fall at visit 1 ranged from 16 to 26 mmHg for active treated group and from 8 to 17 mmHg in controlled.Initial SBP is the only modifier of treatment effect on BP response in the 3 BP lowering drug classes. Age and initial DBP were factors significantly correlated with SBP fall for diuretic and P-blocker. Smokers would receive less SBP fall compare to non-smokers in P-blocker active treated group. There is converse effect of age between the diuretic and P-blocker; older people seem sensitive with diuretic, while young people are sensitive with P-blocker. As to calcium channel antagonist class, only old patients recruited (age>60 years), and age is not a modifier.ConclusionsWe identified the significant modifiers for blood pressure response to pharmacological treatment effect; they are different between drug classes. Other factors including genotype information influencing blood pressure reaction to drugs still were not included in this model. This model need to be further improved and validated.